The treatment of vascular atherosclerotic lesions is a widespread therapy. Such lesions are most often localized at predetermined portions of the blood vessels, of which they cause constrictions or also obstructions. Vascular atherosclerotic lesions are typically treated in angioplasty procedures by means of catheters provided with a balloon.
A catheter provided at the distal end thereof with a balloon is advanced, following a guidewire, to the ostium of the narrowed artery. Once the balloon has been arranged at the artery narrowing, it is repeatedly inflated and deflated. The insufflation, with successive deflation, of the balloon within the artery reduce the extent of the arterial luminal narrowing, and restore a suitable blood flow in the cardiac area, suffering from the stenosis. In some cases, it is necessary to arrange a so-called stent, which provides to maintain the artery patent also after withdrawal of the catheter and the balloon.
In both cases, success of the intervention is not complete. In fact, after a few months, some patients develop a new narrowing of the vessel wall at the intervention point. Such narrowing, known under the name of restenosis, is not due to the formation of new atherosclerotic plaques, but to a cell hyperproliferation process, particularly of the vascular smooth muscle cells, probably due to the dilating action operated by the foreign body, stent or balloon.
It has been observed that restenosis can be treated by coating a stent with a drug having antiproliferative action. Among the drugs usually employed to such aim, paclitaxel (taxol) has proved to be particularly efficient. The drug must be released for a sufficiently long time span, so as to inhibit the cell hyperproliferation process caused by the constant presence of the stent implanted in the vessel. However, the drug also induces an inhibition of the stent endothelization process, which is crucial to avoid the formation of thrombi. For this reasons, the use of a stent with drug elution (“drug eluting stent”) has some drawbacks.
More recently, antiproliferative drug-coated catheter balloons have been proposed. However, in almost all cases, forms of slow release of the drug at the site of intervention after the drug has been transferred from the balloon to the vessel wall have been described.
However, it has been noticed that a drug elution over a prolonged time frame to inhibit the restenosis phenomenon is neither necessary nor desirable, but that it is sufficient, and rather more convenient, a time limited contact between drug and vessel surface, for example, from a few seconds to one minute. These are typically the contact times of a catheter balloon as described before.
The patent publication WO 02/076509 discloses drug-coated catheter balloons releasing such drug in an immediately bioavailable form during the short contact time of the balloon with the vessel wall.
It will be recognized that an approach such as the one described herein above poses completely different problems compared to those previously dealt with. In fact, while a prolonged drug elution can be obtained by various solutions, such as, for example, incorporation of the drug in a polymeric matrix or microcapsules, the immediate release will depend on several factors, of which the main ones are:                The nature of the drug, in particular the hydrophilicity or hydrophobicity thereof;        The form in which the drug is administered, in particular, the crystalline or amorphous form thereof;        The presence of possible excipients or “enhancers”;        Optionally, the nature of the balloon surface on which the drug is deposited.        
In fact, it should be understood that the drug has to be, first of all, released from the balloon to the vessel wall in the very short contact time available during an angioplasty procedure. Once the drug has been released, it has to be absorbed by the cell wall, before the blood flow washes it off. Ideally, it is therefore desirable that the drug absorption occurs concomitantly to the release thereof from the balloon.
However, it is just as well necessary that the drug is retained by the balloon surface in a manner sufficient to resist to all the handling operations which it is subjected to, both during the production step and during the preparation and carrying out of the angioplasty procedure, in any case, before the balloon reaches the site of intervention. This requires a perfect balance of such properties.
Therefore, it is an object of the present invention to provide a catheter balloon coated with a drug which allows an immediate release and bioavailability of the drug at the site of intervention.
It is a further object of the present invention to provide a method of coating of a catheter balloon with a drug in order to reach a good adherence of the drug on the balloon surface and at the same time a fast release of the drug upon contact of the said balloon surface with a blood vessel wall.